Hypokalemic thyrotoxic periodic paralysis is a challenging diagnosis to make as it is rare in non-Asian populations and has a broad differential diagnosis. Thyrotoxic symptoms may be subtle and overlooked. Alternatively, assessing thyroid function helps to distinguish HTPP from other forms of periodic paralysis. Hypokalemic paralysis can be the result of a transcellular shift of potassium (i.e. thyrotoxic periodic paralysis, familial periodic paralysis), a renal loss of potassium (i.e. diuretic use, primary hyperaldosteronism, renal tubular acidosis), or a gastrointestinal loss of potassium (i.e. celiac disease, infectious diarrhea) . The differential diagnosis for periodic paralysis also includes Guillain-Barre syndrome, transverse myelitis, and acute spinal cord compression; bladder and bowel function remain unaffected in HTPP .
HTPP is characterized by hyperthyroidism, muscle paralysis, and hypokalemia without total body potassium deficit . Recent studies suggest that the condition is precipitated by a combination of thyrotoxicosis, environmental factors such as a high carbohydrate load or intense exercise, and an underlying genetic mutation, all of which lead to increased sodium-potassium-adenosine triphosphate (Na/K-ATPase) pump activity . A proposed multifactorial model elucidates Na/K-ATPase pump activity amplification. First, thyroid hormone stimulates Na/K-ATPase activity in skeletal muscle cells . Second, increased physical activity, stress, and thyrotoxicosis all increase catecholamine production. Increased adrenergic response increases Na/K-ATPase activity [8, 10]. Third, hyperinsulinemia leads to worsening of the intracellular shift of potassium in skeletal muscle cells. This explains why the consumption of heavy carbohydrate meals may promote a paralytic attack [11, 12]. Only 2% of patients with hyperthyroidism develop paralysis and as was illustrated by our patient, this proposed model explaining increased activity of Na/K-ATPase may not fully explain the mechanism for HTPP . Although our patient had uncontrolled hyperthyroidism, he gave no history of any precipitating factor such as intense activity or intake of a high carbohydrate meal.
Genetic studies have demonstrated that various gain-of-function and loss-of-function mutations are associated with periodic paralysis . Mutations in Kir2.6 (a potassium ion channel) are seen in up to one-third of patients with HTPP . It is possible that the identification of further gene mutations could help to identify individuals with hyperthyroidism that are at risk for periodic paralysis.
The treatment of an acute presentation of HTPP starts with intravenous or oral supplementation of potassium chloride and use of intravenous or oral propranolol. A retrospective study had demonstrated that patients who received intravenous potassium recovered faster than those who received oral supplementation . However, it should be noted that as potassium is shifted back into the intracellular compartment, excessive potassium replacement may result in rebound hyperkalemia . Propranolol is believed to interfere with the Na/K-ATPase channel and its administration not only mitigates thyrotoxic symptoms, but also addresses the concerns of rebound hyperkalemia and helps to raise the serum levels of potassium and phosphate .
Ultimately, the management of HTPP depends upon adequate treatment of the patient’s hyperthyroidism. Recurrent paralytic episodes can be prevented with strict medication compliance. Patients should avoid precipitating factors such as heavy carbohydrate meals, high-salt diet, alcohol use, and significant physical activity . The use of a non-selective beta-blocker like propranolol is useful until euthyroid status is achieved .
The management of concurrent conditions such as asthma and hyperthyroidism poses a dual risk. The treatment of asthma with beta-2 agonist medications may lead to intracellular shift of potassium. This can precipitate paralysis whereas the treatment of HTPP with beta-blockers may lead to worsening of pulmonary symptoms.